Decreased energy levels can cause and sustain obesity

Abstract

Obesity has reached epidemic proportions and has become one of the major health problems in developed countries. Current theories consider obesity a result of overeating and sedentary life style and most efforts to treat or prevent weight gain concentrate on exercise and food intake. This approach does not improve the situation as may be seen from the steep increase in the prevalence of obesity. This encouraged us to reanalyse existing information and look for biochemical basis of obesity. Our approach was to ignore current theories and concentrate on experimental data which are described in scientific journals and are available from several databases. We developed and applied a Knowledge Discovery in Databases procedure to analyse metabolic data. We began with the contradictory information: in obesity, more calories are consumed than used up, suggesting that obese people should have excess energy. On the other side, obese people experience fatigue and decreased physical endurance that indicates diminished energy supply in the body. The result of our work is a chain of metabolic events leading to obesity. The crucial event is the inhibition of the TCA cycle at the step of aconitase. It disturbs energy metabolism and results in ATP deficiency with simultaneous fat accumulation. Further steps in obesity development are the consequences of diminished energy supply: inhibition of beta-oxidation, leptin resistance, increase in appetite and food intake and a decrease in physical activity. Thus, our theory shows that obesity does not have to be caused by overeating and sedentary life-style but may be the result of the “obese” change in metabolism which is forcing people to overeat and save energy to sustain metabolic functions of cells. This “obese” change is caused by environmental factors that activate chronic low-grade inflammatory process in the body linking obesity with the environment of developed countries.

Introduction

The prevalence of obesity is increasing at a fast rate and obesity has become one of the major health problems in developed countries affecting over a hundred million people world-wide. Obesity is associated with greater risks of high blood pressure, heart disease, osteoarthritis, type 2 diabetes and several other health problems. To improve prevention and treatment of obesity it is necessary to know the mechanisms that cause it. One of the difficulties in obesity research is that obesity may be a symptom of several different diseases or health conditions. Genetic diseases of fat storage and release may cause severe obesity as well as abnormalities in appetite control enzymes, hormonal imbalances or some psychological or neurological factors. Finally, obesity may be a result of overeating without any disease. In this paper we will concentrate on obesity that is induced by environmental factors in otherwise healthy people.

Obesity is a result of positive energy balance: more calories are consumed than used up for oxidation, body building and maintenance. Thus, the common approach to reduce obesity is to either decrease the amount of calorie intake by restricting the amount of food consumed, inhibiting nutrient absorption in the intestine, modulating the activity of hypothalamic centers controlling satiety, or to increase energy spending by increasing physical activity or energy dissipation as heat (Keller et al., 1997; Kopecky, 1998). However, obese people very often experience tiredness (Lean, 2000) even without sleep apnea (Vgontzas et al., 1998). During physical exercise they get fatigued faster than lean people (Ardevol et al., 1998; Mattsson et al., 1997) and have decreased exercise capacity (Hulens et al., 2001). Thus, it seems that obese people have at the same time too much and too little energy. The apparent paradox may be explained by considering what metabolic energy is. The currency of free energy in living organisms is adenosine triphosphate (ATP). Nutrients from food are metabolized to fuel and next, either to ATP—and only then they become equivalents of energy—or become precursors of fat or proteins. Fat and proteins may be metabolized to ATP but this is not an automatic conversion and involves several metabolic steps. The schematic distribution of fuel between fat and energy in healthy and obese people is shown in Fig. 1. A common concept in the area of obesity research is an equalization of fat with energy. It is based on a silent and false assumption that steps involved in fat synthesis and in beta-oxidation are never disturbed. Fat is the storage of fuel and only after it is metabolized to ATP does it become energy. Thus, the correct statement is that obese individuals have a deficit of energy in the form of ATP with simultaneous overproduction of fat. Therefore, the logical question is: why in some people, is the energy from food diverted to fat synthesis before all of the energetic needs in the body are satisfied?

To address this question we applied a theoretical approach which belongs to a Knowledge Discovery in Databases (KDD) methodology. KDD is a process of identifying relationships between data that exist in databases but are not apparent because of the large number of data (Fayyad et al., 1996). These discovered relationships represent a new knowledge, a theory about the rules governing the data, derived from already existing data. The process involves human decision-making and computer technology. KDD is used in many different areas of science and business. An example of the KDD application to genomic and proteomic databases is a work done by Satou et al. (1997) with the purpose of finding correlations between protein sequence, structure and function. In this application the data mining process was based on the discovery of association rules and the verification of the rules would be a prediction of protein structure or function from the sequence. The data included information on sequence, secondary structure and EC numbers as indicators of function. Algorithms were used that iteratively perform searches until similar structures were found. KDD was able to identify substructures that were unrelated to the active site but common to proteins which had the same function. We used KDD to discover new relationships in metabolism. This research has allowed us to find out which metabolic disturbances lead to obesity and to formulate a theory for environmentally caused obesity supported by experimental data described already in the scientific literature.